Recurrent anaphylaxis-like episodes revealing RYR1-associated malignant hyperthermia susceptibility: a case report

Background Malignant hyperthermia (MH) is a rare pharmacogenetic disorder associated with variants in the RYR1 , CANCA1S , or STAC3 genes that result in excessive and uncontrolled intracellular calcium release in response to triggering stimuli. MH is characterized by generalized muscle rigidity, tachycardia, increased body temperature, and acidosis. Anaphylaxis is a severe, rapidly progressive hypersensitivity reaction primarily driven by mast cell and basophil degranulation. Degranulation releases preformed inflammatory mediators such as histamine and upregulates synthesis of others, namely leukotrienes, prostaglandins, and cytokines, ultimately yielding multi-system involvement characteristic of anaphylaxis. While MH is classically triggered by anesthetic gases, anaphylaxis is associated with a broad range of triggers, including foods, medications, insect venoms, and less commonly exercise and environmental heat exposure. Case presentation We describe a case of a patient experiencing recurrent anaphylaxis-like symptomatology including muscle rigidity, weakness, dystonic posturing, and gastrointestinal and cutaneous symptoms, appearing to be exacerbated by food intake. Subsequent allergy and immunology investigation for new-onset food allergy and anaphylaxis, including skin-prick testing, serum-specific IgE, and tryptase, did not show evidence of allergy. Neuromuscular, inflammatory, and autoimmune evaluation were also unable to establish a diagnosis. Genetic testing revealed a heterozygous RYR1 variant of uncertain significance, however empirical IV dantrolene treatment resulted in rapid symptom resolution. The RYR1 variant of uncertain significance and temporal improvement following dantrolene raised concern for possible malignant hyperthermia susceptibility but did not establish susceptibility or demonstrate that the recurrent episodes represented non-anesthetic malignant hyperthermia. Discussion and conclusions While there is an overlap of triggering factors and clinical features in MH and anaphylaxis, our case features gastrointestinal and dermatologic involvement alongside food as a trigger, features consistent with anaphylaxis but uncharacteristic of MH. To our knowledge, a presentation of RYR1 -associated malignant hyperthermia susceptibility characterized by recurrent anaphylaxis-like features that are exacerbated by food intake is not one that has been described in published literature.